The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation
Abstract
Insulin receptor substrates (IRS) serine phosphorylation is a time-controlled physiological feedback mechanism in insulin signaling that is hijacked by metabolic and inflammatory stresses to promote insulin resistance. Kinases, including IKKbeta, JNK, ERK, mTOR, and S6K, activated by the inducers of insulin resistance induce uncontrolled IRS serine phosphorylation. Studies with genetically modified mice reveal that these kinases integrate signals from metabolic and inflammatory stresses in adipose tissue, liver, and hypothalamus leading to peripheral and central insulin resistance. Moreover, IKKbeta/NF-kappaB and JNK1 pathways in myeloid cells represent a core mechanism involved in inflammation linked to obesity. These kinases are thus potential drug targets against insulin resistance and the targeting of the IKKbeta/NF-kappaB or the JNK pathway may evolve into future diabetes medication.
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“Increased stress kinase activity also has been implicated in contribute to the serine phosphorylation of IRS-1 and subsequent impairment tyrosine phosphorylation [177, 178].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [177]
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1 retracted
Herschkovitz, A., Liu, Y., Ilan, E., Ronen, D., Boura‐Halfon, S., & Zick, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610949200 · Cited by 98
RetractedInflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Molecular mechanisms of mTOR-mediated translational control
Ma, X. M., & Blenis, J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2672 · Cited by 2,558
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
Obesity, Inflammation, and Insulin Resistance
Shoelson, S. E., Herrero, L., & Naaz, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.059 · Cited by 1,806
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677
The IKK NF-κB system: a treasure trove for drug development
Karin, M., Yamamoto, Y., & Wang, Q. M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1279 · Cited by 1,364
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Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871
ERK1/2 MAP kinases: Structure, function, and regulation
Roskoski, R. J. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.04.005 · Cited by 1,719
Diabetes mellitus: The epidemic of the century
Kharroubi, A. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i6.850 · Cited by 1,352
The insulin and insulin-like growth factor receptor family in neoplasia: an update
Pollak, M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3215 · Cited by 1,116
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“However, as reviewed herein and elsewhere [5, 6], unique phospho-S/T on IRS1 can have negative (or positive) effects on insulin signalling that are currently unexplainable in either structural terms or by a requirement for multiple phosphorylation.”
BackgroundInfluential
Metadata
- Authors
- Tanti, J.-F., & Jager, J.
- Affiliations
- Inserm (FR)
- Corresponding author
- Tanti, Jean-François
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 9
- Issue
- 6
- Pages
- 753-762
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2001649002
- Cited by
- 430
- References
- 74
- Citations by year
- 2026: 19 · 2025: 14 · 2024: 8 · 2023: 17 · 2022: 29 · 2021: 24 · 2020: 17 · 2019: 20 · 2018: 23 · 2017: 28 · 2016: 32 · 2015: 36 · 2014: 41 · 2013: 41 · 2012: 38
- FWCI
- 18.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- insulin resistance, insulin receptor substrate, serine phosphorylation, insulin signaling, IKKβ, NF-κB, JNK, ERK, mTOR, S6K, inflammation, obesity, adipose tissue, liver, hypothalamus, myeloid cells
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin Resistance, Models, Biological, Phosphorylation, Signal Transduction, NF-kappa B, Drug Delivery Systems, Protein Serine-Threonine Kinases, Mice, Knockout, Intracellular Signaling Peptides and Proteins, Mice, I-kappa B Kinase, Insulin Receptor Substrate Proteins, TOR Serine-Threonine Kinases
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